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Tsvetkova A, Ozerov IV, Pustovalova M, et al. γH2AX, 53BP1 and Rad51 protein foci changes in mesenchymal stem cells during prolonged X-ray irradiation. Oncotarget. 2017;8(38):64317-64329doi: 10.18632/oncotarget.19203.
Tsvetkova, A., Ozerov, I. V., Pustovalova, M., Grekhova, A., Eremin, P., Vorobyeva, N., Eremin, I., Pulin, A., Zorin, V., Kopnin, P., Leonov, S., Zhavoronkov, A., Klokov, D., & Osipov, A. N. (2017). γH2AX, 53BP1 and Rad51 protein foci changes in mesenchymal stem cells during prolonged X-ray irradiation. Oncotarget, 8(38), 64317-64329. https://doi.org/10.18632/oncotarget.19203
Tsvetkova, Anastasia, et al. "γH2AX, 53BP1 and Rad51 protein foci changes in mesenchymal stem cells during prolonged X-ray irradiation." Oncotarget vol. 8,38 (2017): 64317-64329. doi: https://doi.org/10.18632/oncotarget.19203
Tsvetkova A, Ozerov IV, Pustovalova M, Grekhova A, Eremin P, Vorobyeva N, Eremin I, Pulin A, Zorin V, Kopnin P, Leonov S, Zhavoronkov A, Klokov D, Osipov AN. γH2AX, 53BP1 and Rad51 protein foci changes in mesenchymal stem cells during prolonged X-ray irradiation. Oncotarget. 2017 Jul 12;8(38):64317-64329. doi: 10.18632/oncotarget.19203. eCollection 2017 Sep 08. PMID: 28969073; PMCID: PMC5610005.
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Oncotarget. 2017 Jul 12;8(38):64317-64329. doi: 10.18632/oncotarget.19203. eCollection 2017 Sep 08.

γH2AX, 53BP1 and Rad51 protein foci changes in mesenchymal stem cells during prolonged X-ray irradiation.

Oncotarget

Anastasia Tsvetkova, Ivan V Ozerov, Margarita Pustovalova, Anna Grekhova, Petr Eremin, Natalia Vorobyeva, Ilya Eremin, Andrey Pulin, Vadim Zorin, Pavel Kopnin, Sergey Leonov, Alex Zhavoronkov, Dmitry Klokov, Andreyan N Osipov

Affiliations

  1. Lomonosov Moscow State University, Moscow 119991, Russia.
  2. State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC-FMBC), Moscow 123098, Russia.
  3. Insilico Medicine, Inc, ETC, Johns Hopkins University, Baltimore, Maryland 21218, USA.
  4. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow 119991, Russia.
  5. Emanuel Institute for Biochemical Physics, Russian Academy of Sciences, Moscow 119991, Russia.
  6. Federal State Budgetary Institution "Central Clinical Hospital with Outpatient Health Center" of The Business Administration for The President of The Russian Federation, Moscow 121359, Russia.
  7. PJSC Human Stem Cells Institute, Moscow 119333, Russia.
  8. N.N. Blokhin Cancer Research Center, Moscow 115478, Russia.
  9. Moscow Institute of Physics and Technology, Moscow 141700, Russia.
  10. Canadian Nuclear Laboratories, Chalk River, Ontario K0J1P0, Canada.

PMID: 28969073 PMCID: PMC5610005 DOI: 10.18632/oncotarget.19203

Abstract

At high exposure levels ionizing radiation is a carcinogen. Little is known about how human stem cells, which are known to contribute to tumorigenesis, respond to prolonged radiation exposures. We studied formation of DNA double strand breaks, accessed as γH2AX and 53BP1 foci, in human mesenchymal stem cells (MSCs) exposed to either acute (5400 mGy/h) or prolonged (270 mGy/h) X-irradiation. We show a linear γH2AX and 53BP1 dose response for acute exposures. In contrast, prolonged exposure resulted in a dose-response curve that had an initial linear portion followed by a plateau. Analysis of Rad51 foci, as a marker of homologous recombination, in cells exposed to prolonged irradiation revealed a threshold in a dose response. Using Ki67 as a marker of proliferating cells, we show no difference in the γH2AX distribution in proliferating vs. quiescent cells. However, Rad51 foci were found almost exclusively in proliferating cells. Concurrent increases in the fraction of S/G2 cells were detected in cells exposed to prolonged irradiation by scoring CENPF-positive cells. Our data suggest that prolonged exposure of MSCs to ionizing radiation leads to cell cycle redistribution and associated activation of homologous recombination. Also, proliferation status may significantly affect the biological outcome, since homologous repair is not activated in resting MSCs.

Keywords: DNA double strand breaks; DNA repair; X-rays; continuous irradiation; mesenchymal stem cells

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no conflicts of interest.

References

  1. Arh Hig Rada Toksikol. 2014 Sep 29;65(3):251-7 - PubMed
  2. Mutat Res. 2013 Aug 30;756(1-2):141-5 - PubMed
  3. Stem Cells. 2013 Apr;31(4):800-7 - PubMed
  4. Ann ICRP. 2007;37(2-4):1-332 - PubMed
  5. Environ Health Perspect. 2012 Aug;120(8):1130-6 - PubMed
  6. Radiat Res. 2014 Nov;182(5):463-74 - PubMed
  7. Radiat Res. 2016 Jul;186(1):17-26 - PubMed
  8. Dose Response. 2007 Sep 10;5(4):284-91 - PubMed
  9. Oncotarget. 2015 Sep 29;6(29):27275-87 - PubMed
  10. Clin Cancer Res. 2010 Dec 15;16(24):6159-68 - PubMed
  11. Radiat Res. 2016 Jun;185(6):580-90 - PubMed
  12. J Radiat Res. 2011;52(3):380-6 - PubMed
  13. Integr Environ Assess Manag. 2011 Jul;7(3):371-3 - PubMed
  14. Environ Mol Mutagen. 2015 Jul;56(6):491-504 - PubMed
  15. Am J Pathol. 2010 Jun;176(6):2584-494 - PubMed
  16. PLoS One. 2011;6(12):e28559 - PubMed
  17. Stem Cells Dev. 2010 Nov;19(11):1699-711 - PubMed
  18. Cytotherapy. 2016 Mar;18(3):384-401 - PubMed
  19. Carcinogenesis. 2002 May;23(5):687-96 - PubMed
  20. Environ Health Toxicol. 2016 Jan 20;31:e2016001 - PubMed
  21. Radiat Environ Biophys. 2015 Nov;54(4):379-401 - PubMed
  22. Int J Mol Sci. 2013 Jul 01;14(7):13719-26 - PubMed
  23. Exp Hematol. 2004 Nov;32(11):1088-96 - PubMed
  24. Curr Alzheimer Res. 2012 Mar;9(3):278-89 - PubMed
  25. Mutagenesis. 2000 Jul;15(4):289-302 - PubMed
  26. Radiat Prot Dosimetry. 2015 Jul;165(1-4):17-21 - PubMed
  27. Ann ICRP. 2015 Dec;44(3-4):7-357 - PubMed
  28. PLoS One. 2013 Jul 11;8(7):e69061 - PubMed
  29. Nonlinearity Biol Toxicol Med. 2004 Jul;2(3):223-32 - PubMed
  30. Mol Cell. 2017 May 4;66(3):306-319 - PubMed
  31. Radiat Res. 2013 May;179(5):501-10 - PubMed
  32. Int J Radiat Biol. 2007 May;83(5):319-29 - PubMed
  33. Respir Investig. 2013 Sep;51(3):128-33 - PubMed
  34. Cell Cycle. 2017 Feb;16(3):251-258 - PubMed
  35. Yale J Biol Med. 2013 Dec 13;86(4):453-61 - PubMed
  36. Genes Cells. 2016 Jul;21(7):789-97 - PubMed
  37. J Periodontol. 2010 Jun;81(6):917-25 - PubMed
  38. Radiat Res. 2010 Dec;174(6):833-9 - PubMed
  39. Transfusion. 2014 May;54(5):1418-37 - PubMed
  40. Stem Cells. 2016 Apr;34(4):1011-26 - PubMed
  41. Oncotarget. 2015 Sep 29;6(29):26876-85 - PubMed
  42. Nat Genet. 2001 Mar;27(3):247-54 - PubMed
  43. Biomed Mater. 2014 Aug 28;9(5):055005 - PubMed
  44. Lancet. 2015 Aug 1;386(9992):469-78 - PubMed
  45. Redox Biol. 2013 Jan 19;1:153-62 - PubMed
  46. Mutat Res. 2010 Apr-Jun;704(1-3):132-41 - PubMed
  47. Nature. 2009 Oct 22;461(7267):1071-8 - PubMed
  48. Chromosoma. 2006 Aug;115(4):288-95 - PubMed
  49. Mutat Res Rev Mutat Res. 2014 Feb 22;:null - PubMed
  50. J Radiol Prot. 2002 Sep;22(3A):A21-5 - PubMed

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